TY - JOUR
T1 - Plasma microRNA profiles for bladder cancer detection
AU - Adam, Liana
AU - Wszolek, Matthew F.
AU - Liu, Chang Gong
AU - Jing, Wang
AU - Diao, Lixia
AU - Zien, Alexander
AU - Zhang, Jitao D.
AU - Jackson, David
AU - Dinney, Colin P.N.
N1 - Funding Information:
The authors thank T. Nicola for kindly providing plasma samples from noncancerous patients, S. Ajibode for technical assistance, and C. Calin for helpful discussions on the manuscript. This work was supported by Molecular Health, GmbH , through a sponsored research agreement with the UT MD Anderson Cancer Center and by the National Institutes of Health through MD Anderson's Cancer Center Support grant CA016672 , NIH/NCI GU SPORE (P50 CA91846-04) grant.
PY - 2013/11
Y1 - 2013/11
N2 - Background: Bladder cancer (BC) is a burdensome disease with significant morbidity, mortality, and cost. The development of novel plasma-based biomarkers for BC diagnosis and surveillance could significantly improve clinical outcomes and decrease health expenditures. Plasma miRNAs are promising biomarkers that have yet to be rigorously investigated in BC. Objective: To determine the feasibility and efficacy of detecting BC with plasma miRNA signatures. Materials and methods: Plasma miRNA was isolated from 20 patients with bladder cancer and 18 noncancerous controls. Samples were analyzed with a miRNA array containing duplicate probes for each miRNA in the Sanger database. Logistic regression modeling was used to optimize diagnostic miRNA signatures to distinguish between muscle invasive BC (MIBC), non-muscle-invasive BC (NMIBC) and noncancerous controls. Results: Seventy-nine differentially expressed plasma miRNAs (local false discovery rate [FDR] <0.5) in patients with or without BC were identified. Some diagnostically relevant miRNAs, such as miR-200b, were up-regulated in MIBC patients, whereas others, such as miR-92 and miR-33, were inversely correlated with advanced clinical stage, supporting the notion that miRNAs released in the circulation have a variety of cellular origins. Logistic regression modeling was able to predict diagnosis with 89% accuracy for detecting the presence or absence of BC, 92% accuracy for distinguishing invasive BC from other cases, 100% accuracy for distinguishing MIBC from controls, and 79% accuracy for three-way classification between MIBC, NIMBC, and controls. Conclusions: This study provides preliminary data supporting the use of plasma miRNAs as a noninvasive means of BC detection. Future studies will be required to further specify the optimal plasma miRNA signature, and to apply these signatures to clinical scenarios, such as initial BC detection and BC surveillance.
AB - Background: Bladder cancer (BC) is a burdensome disease with significant morbidity, mortality, and cost. The development of novel plasma-based biomarkers for BC diagnosis and surveillance could significantly improve clinical outcomes and decrease health expenditures. Plasma miRNAs are promising biomarkers that have yet to be rigorously investigated in BC. Objective: To determine the feasibility and efficacy of detecting BC with plasma miRNA signatures. Materials and methods: Plasma miRNA was isolated from 20 patients with bladder cancer and 18 noncancerous controls. Samples were analyzed with a miRNA array containing duplicate probes for each miRNA in the Sanger database. Logistic regression modeling was used to optimize diagnostic miRNA signatures to distinguish between muscle invasive BC (MIBC), non-muscle-invasive BC (NMIBC) and noncancerous controls. Results: Seventy-nine differentially expressed plasma miRNAs (local false discovery rate [FDR] <0.5) in patients with or without BC were identified. Some diagnostically relevant miRNAs, such as miR-200b, were up-regulated in MIBC patients, whereas others, such as miR-92 and miR-33, were inversely correlated with advanced clinical stage, supporting the notion that miRNAs released in the circulation have a variety of cellular origins. Logistic regression modeling was able to predict diagnosis with 89% accuracy for detecting the presence or absence of BC, 92% accuracy for distinguishing invasive BC from other cases, 100% accuracy for distinguishing MIBC from controls, and 79% accuracy for three-way classification between MIBC, NIMBC, and controls. Conclusions: This study provides preliminary data supporting the use of plasma miRNAs as a noninvasive means of BC detection. Future studies will be required to further specify the optimal plasma miRNA signature, and to apply these signatures to clinical scenarios, such as initial BC detection and BC surveillance.
KW - Bladder cancer
KW - Diagnostic
KW - MicroRNAs
KW - Plasma
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U2 - 10.1016/j.urolonc.2012.06.010
DO - 10.1016/j.urolonc.2012.06.010
M3 - Article
C2 - 22863868
AN - SCOPUS:84886233388
SN - 1078-1439
VL - 31
SP - 1701
EP - 1708
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 8
ER -